July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Early retinal and cerebral deficits in a high fat diet + low dose STZ rat model of Type II diabetes
Author Affiliations & Notes
  • Rachael S Allen
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
    Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Andrew Feola
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
    Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Kyle Christopher Chesler
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
    Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Cara Motz
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
  • Monica M Coulter
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
  • Peter M Thule
    Section Endocrinology and Metabolism, Atlanta VA Medical Center, Decatur, Georgia, United States
    Section Endocrinology and Metabolism, Emory University School of Medicine, Atlanta, Georgia, United States
  • Jeffrey H Boatright
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
    Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States
  • Machelle T Pardue
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
    Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Rachael Allen, None; Andrew Feola, None; Kyle Chesler, None; Cara Motz, None; Monica Coulter, None; Peter Thule, None; Jeffrey Boatright, None; Machelle Pardue, None
  • Footnotes
    Support  This material is based upon work supported by the Department of Veterans Affairs (Rehabilitation R&D Service Career Development Award-1 (RX002111) to R.S.A; Rehabilitation R&D Service Merit Award and Research Career Scientist Award to M.T.P.), Research to Prevent Blindness (Emory), NIH NEI P30EY06360 (Emory), and Foundation Fighting Blindness.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5991. doi:
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    • Get Citation

      Rachael S Allen, Andrew Feola, Kyle Christopher Chesler, Cara Motz, Monica M Coulter, Peter M Thule, Jeffrey H Boatright, Machelle T Pardue; Early retinal and cerebral deficits in a high fat diet + low dose STZ rat model of Type II diabetes. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5991.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The high fat diet (HFD) + low dose STZ model was reported as a new model of Type II diabetes by Reed et al., 2000. In this model, rats are fed a high fat diet (40% kcal fat for 4 weeks), causing insulin resistance by 2 weeks. Rats are then given a single low dose of STZ (30 mg/kg vs. the 100 mg/kg used to create Type I diabetic rats), resulting in elevated blood glucose (>160 mg/dL compared with >250 mg/dL in the STZ model of Type I diabetes). Here, we examined early changes in retinal, cerebral, and metabolic function in this Type II diabetic model for 8 weeks.

Methods : Adult male Long Evans rats were assigned to one of the following groups: HFD+STZ (n = 6), HFD only (n = 5), and control rats (n = 4) that received normal rat chow. Visual function using optomotor response (OMR) was assessed every two weeks beginning just prior to HFD. Retinal function using electroretinogram oscillatory potentials (OPs) and cognitive function using Y-maze were assessed every four weeks. A panel of metabolic assessments, including measures of weight, fed and fasted blood glucose, insulin and glucose tolerance, and ELISA for blood insulin levels were also performed.

Results : Using our panel of metabolic assessments, we were able to determine which HFD+STZ rats exhibit a Type II phenotype (moderately high blood glucose levels and impaired glucose tolerance with insulin levels and weight gain close to control levels). In addition to metabolic changes, HFD+STZ rats showed deficits in OMR at 4 weeks post-STZ (9% reduction in spatial frequency) and delays in dim flash OP implicit times (12% delay) at 8 weeks. HFD only rats also showed OMR (5% reduction) and OP deficits (9% delay), but not to the same degree as HFD+STZ rats. Y-maze deficits were not observed in HFD+STZ rats by 8 weeks but may appear later in this model.

Conclusions : HFD+STZ rats exhibit a moderate diabetic state, while still showing retinal deficits typical of diabetes. This model may be more similar to Type II diabetes in patients. An observable retinal deficit at the 4-week time point matches our data in Type I (high dose STZ) and Type II (Goto-Kakizaki) models, indicating that 4 weeks of hyperglycemia induces retinal dysfunction regardless of the cause.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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